Cloning and characterization of a naturally occurring soluble form of TGF-β type I receptor.

نویسنده

  • Mary E Choi
چکیده

Transforming growth factor-β1 (TGF-β1) has been implicated to play an important role both in the process of normal development and in the pathogenesis of a wide variety of disease processes, including those of the kidney. TGF-β1 regulates diverse cellular functions via a heteromeric signaling complex of two transmembrane serine/threonine kinase receptors (types I and II). Several distinct type I receptors have been described and are thought to determine specificity of the TGF-β response and confer multifunctionality. This report reveals the cloning of a novel, naturally occurring soluble form of TGF-β type I receptor, designated sTβR-I, from a rat kidney cDNA library. In vivo expression of a mRNA transcript encoding the sTβR-I, which lacks the transmembrane and cytoplasmic domains, is confirmed by RT-PCR followed by Southern blot analysis and by RNase protection assay. The sTβR-I mRNA abundance is greater in the neonatal rat kidney compared with the adult rat kidney. Furthermore, sTβR-I is a functional protein capable of binding TGF-β1 ligands in the presence of a TGF-β type II receptor on the cell surface, as determined by affinity cross-linking with 125I-labeled TGF-β1. Studies using p3TP-Lux reporter construct reveal that this novel protein may function as a potentiator of TGF-β signaling. The discovery of a sTβR-I provides an additional level of complexity to the TGF-β receptor system.

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عنوان ژورنال:
  • American journal of physiology. Renal physiology

دوره 276 1  شماره 

صفحات  -

تاریخ انتشار 1999